Department of Gastroenterology, Changzhou Hospital of Traditional Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Changzhou, China.
The First College of Clinical Medicine, Henan University of Chinese Medicine, Zhengzhou, China.
Front Immunol. 2024 Sep 13;15:1431990. doi: 10.3389/fimmu.2024.1431990. eCollection 2024.
Previous research has demonstrated an association between gut microbiota and immune status with the development of several diseases. However, whether these factors contribute to polyps remains unclear. This study aims to use Mendelian randomization (MR) to investigate the causal relationship between gut microbiota and 4 types of polyps (nasal, gallbladder, colon, and gastric polyps), as well as to analyze the mediating role of immune traits.
This study utilized large-scale GWAS meta-analyses of gut microbiota (MiBioGen Consortium), 731 immune traits, and 4 types of polyps (one from the FinnGen Consortium and three from the NBDC Human Database). Univariate MR with the inverse variance weighted (IVW) estimation method was employed as the primary analytical approach. A two-step MR analysis was performed to identify potential mediating immune traits. Additionally, multivariable MR approach based on Bayesian model averaging (MR-BMA) was employed to further prioritize gut microbiota and immune traits associated with polyp development.
Based on IVW method in univariate MR analysis, we identified 39 gut microbial taxa and 135 immune traits significantly causally associated with at least one type of polyp. For nasal polyps, 13 microbial taxa and 61 immune traits were causally associated. After false discovery rate (FDR) correction, CD3 on Central Memory CD8 T cells and CD3 on CD4 regulatory T cells remained significant. MR-BMA identified 4 gut microbial taxa and 4 immune traits as high priority. For gallbladder polyps, 9 microbial taxa and 30 immune traits were causally associated. MR-BMA identified 8 microbial taxa and 6 immune traits as higher importance. For colon polyps, 6 microbial taxa and 21 immune traits were causally associated. MR-BMA identified 4 microbial taxa and 3 immune traits as higher importance. For gastric polyps, 12 microbial taxa and 33 immune traits were causally associated. remained significant after FDR correction, and MR-BMA identified 7 gut microbial taxa and 6 immune traits as high priority. We identified 16 causal pathways with mediator directions consistent with the direction of gut microbiome-polyp association. Of these, 6 pathways were associated with the mechanism of nasal polyps, 1 with gallbladder polyps, 2 with colon polyps, and 7 with gastric polyps.
Our findings shed light on the causal relationships between gut microbiota, immune traits, and polyp development, underscoring the crucial roles of gut microbiota and immune status in polypogenesis. Furthermore, these findings suggest potential applications in polyp prevention, early screening, and the development of effective strategies to reduce polyp risk.
先前的研究表明，肠道微生物群与免疫状态与多种疾病的发展有关。然而，这些因素是否与息肉的形成有关尚不清楚。本研究旨在使用孟德尔随机化（MR）方法来研究肠道微生物群与 4 种息肉（鼻息肉、胆囊息肉、结肠息肉和胃息肉）之间的因果关系，并分析免疫特征的中介作用。
本研究利用大规模的肠道微生物组（MiBioGen 联盟）、731 种免疫特征和 4 种息肉（一个来自 FinnGen 联盟，三个来自 NBDC 人类数据库）的全基因组关联研究荟萃分析。采用单变量 MR 分析，采用逆方差加权（IVW）估计方法。采用两步 MR 分析来确定潜在的中介免疫特征。此外，基于贝叶斯模型平均（MR-BMA）的多变量 MR 方法用于进一步确定与息肉形成相关的肠道微生物群和免疫特征的优先级。
基于单变量 MR 分析中的 IVW 方法，我们确定了 39 种肠道微生物群和 135 种免疫特征与至少一种类型的息肉有因果关系。对于鼻息肉，有 13 种微生物群和 61 种免疫特征与息肉的形成有因果关系。经错误发现率（FDR）校正后，中央记忆 CD8 T 细胞上的 CD3 和 CD4 调节性 T 细胞上的 CD3 仍然显著。MR-BMA 确定了 4 种肠道微生物群和 4 种免疫特征为高优先级。对于胆囊息肉，有 9 种微生物群和 30 种免疫特征与息肉的形成有因果关系。MR-BMA 确定了 8 种肠道微生物群和 6 种免疫特征为更高优先级。对于结肠息肉，有 6 种微生物群和 21 种免疫特征与息肉的形成有因果关系。MR-BMA 确定了 4 种肠道微生物群和 3 种免疫特征为更高优先级。对于胃息肉，有 12 种微生物群和 33 种免疫特征与息肉的形成有因果关系。经 FDR 校正后，仍有 5 种与息肉的形成有因果关系，MR-BMA 确定了 7 种肠道微生物群和 6 种免疫特征为高优先级。我们确定了 16 条具有与肠道微生物群-息肉关联方向一致的中介作用方向的因果途径。其中，6 条途径与鼻息肉的发病机制有关，1 条与胆囊息肉有关，2 条与结肠息肉有关，7 条与胃息肉有关。
本研究结果揭示了肠道微生物群、免疫特征与息肉发生之间的因果关系，强调了肠道微生物群和免疫状态在息肉发生中的重要作用。此外，这些发现为息肉的预防、早期筛查以及开发降低息肉风险的有效策略提供了潜在的应用价值。
